Type Checking Research Articles

Tolerability, safety, and pharmacokinetics of GR1603 injection in healthy subjects: a randomized, double-blind, placebo-controlled single-dose escalation clinical trial

ABSTRACT Background GR1603 is a monoclonal antibody targeting the type I interferon receptor. The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and pharmacodynamics of GR1603 in healthy volunteers. Methods Healthy adults (≥18 years old) were enrolled in a placebo control, dose-escalation Phase I clinical trial receiving a single injectable dose of GR1603. Follow-up was 12 weeks. Adverse event (AE) profiles, vital signs, and blood samples were collected for assessment of safety, PK, and expression of type I interferon inducible genes. Results Of the 46 subjects, 44 completed treatment. In the experimental group of 34 subjects (mean age 26.6 years), 30 experienced treatment-emergent adverse events (TEAEs), with a total of 102 occurrences, resulting in an incidence rate of 88.2%. The most commonly reported drug-related AEs were upper respiratory tract infection (17.6%), all of which were ≤ grade 2. GR1603 exhibits non-linear PK in the dose range of 0.1 mg/kg to 9 mg/kg. All samples were negative for anti-drug antibodies before and after dosing. The degrees of IFN gene signature were significantly inhibited in the higher dose groups. Conclusion The safety/tolerability, PK and exploratory metrics observed in this study support further clinical development of GR1603.

Correct and Complete Type Checking and Certified Erasure for Coq, in Coq

Coq is built around a well-delimited kernel that performs type checking for definitions in a variant of the Calculus of Inductive Constructions ( CIC ). Although the metatheory of CIC is very stable and reliable, the correctness of its implementation in Coq is less clear. Indeed, implementing an efficient type checker for CIC is a rather complex task, and many parts of the code rely on implicit invariants which can easily be broken by further evolution of the code. Therefore, on average, one critical bug has been found every year in Coq . This paper presents the first implementation of a type checker for the kernel of Coq (without the module system, template polymorphism and η -conversion), which is proven sound and complete in Coq with respect to its formal specification. Note that because of Gödel’s second incompleteness theorem, there is no hope to prove completely the soundness of the specification of Coq inside Coq (in particular strong normalization), but it is possible to prove the correctness and completeness of the implementation assuming soundness of the specification, thus moving from a trusted code base (TCB) to a trusted theory base (TTB) paradigm. Our work is based on the MetaCoq project which provides meta-programming facilities to work with terms and declarations at the level of the kernel. We verify a relatively efficient type checker based on the specification of the typing relation of the Polymorphic, Cumulative Calculus of Inductive Constructions ( PCUIC ) at the basis of Coq . It is worth mentioning that during the verification process, we have found a source of incompleteness in Coq ’s official type checker, which has then been fixed in Coq 8.14 thanks to our work. In addition to the kernel implementation, another essential feature of Coq is the so-called extraction mechanism: the production of executable code in functional languages from Coq definitions. We present a verified version of this subtle type and proof erasure step, therefore enabling the verified extraction of a safe type checker for Coq in the future.

Current role of focal therapy in prostate cancer.

Thanks to the improved accuracy of multiparametric Magnetic Resonance Imaging (mpMRI) to detect and localize the dominant index lesion on prostate cancer (PCa), the concept of minimally invasive focal treatments (FT) has gained popularity. Nevertheless, although high-quality evidence that FT has favorable functional outcomes, definitive proof of its oncological effectiveness compared to standard treatments remains underreported. This study aims to explore the efficacy, safety, oncologic and functional outcomes of different type of FT for PCa. A non-systematic literature review was conducted by searching on PubMed "prostate cancer" AND "focal treatment" OR "HIFU" OR "irreversible electroporation" OR "cryoablation" OR "focal laser ablation." Overall, 22 articles published in English literature from 2018 to 2023 describing FT techniques for PCa were included. Related to the field ablated, focal therapies include hemiablation (half gland), focal ablation (zonal-base) or targeted therapy (lesion-based). FT modalities can be categorized in thermal and non-thermal energy: thermal energy techniques include high-intensity focused ultrasound (HIFU), cryotherapy, radiofrequency ablation (RFA), and focal laser ablation (FLA). Focal brachytherapy, irreversible electroporation (IRE), and vascular-targeted photodynamic therapy (VTP) are classified as non-thermal ablation. Each focal ablative treatments could be promising alternative to conventional radical therapies to treat PCa in term of mid-term oncologic and functional outcomes, however, limited data are available in comparison with standardized radical treatments. HIFU and Cryo are the most studied techniques and seem to be superior to radical treatments in term of functional outcomes despite associated with higher recurrence and retreatment rate. Current evidences of oncologic and functional outcomes of FT are based mainly on retrospective, non-comparative and single center studies. Thus, none of the focal therapies available should be considered safe alternative to standardized treatments in routine practice and should be offered only for well selected PCa patients with low or at least favorable-intermediate risk disease, unfit for radical options.

A Logical Approach to Type Soundness

Type soundness, which asserts that “well-typed programs cannot go wrong,” is widely viewed as the canonical theorem one must prove to establish that a type system is doing its job. It is commonly proved using the so-called syntactic approach (also known as progress and preservation ), which has had a huge impact on the study and teaching of programming language foundations. Unfortunately, syntactic type soundness is a rather weak theorem. It only applies to programs that are well typed in their entirety and thus tells us nothing about the many programs written in “safe” languages that make use of “unsafe” language features. Even worse, it tells us nothing about whether type systems achieve one of their main goals: enforcement of data abstraction. One can easily define a language that enjoys syntactic type soundness and yet fails to support even the most basic modular reasoning principles for abstraction mechanisms like closures, objects, and abstract data types. Given these concerns, we argue that programming languages researchers should no longer be satisfied with proving syntactic type soundness and should instead start proving semantic type soundness , a more useful theorem that captures more accurately what type systems are actually good for. Semantic type soundness is an old idea—Milner’s original account of type soundness from 1978 was semantic—but it fell out of favor in the 1990s due to limitations and complexities of denotational models. In the succeeding decades, thanks to a series of technical advances—notably, step-indexed Kripke logical relations constructed over operational semantics and higher-order concurrent separation logic as consolidated in the Iris framework in Coq—we can now build (machine-checked) semantic soundness proofs at a much higher level of abstraction than was previously possible. The resulting “logical” approach to semantic type soundness has already been employed to great effect in a number of recent papers, but those papers typically (a) concern advanced problem scenarios that complicate the presentation, (b) assume significant prior knowledge of the reader, and (c) suppress many details of the proofs. Here, we aim to provide a gentler, more pedagogically motivated introduction to logical type soundness, targeted at a broader audience that may or may not be familiar with logical relations and Iris. As a bonus, we also show how logical type soundness proofs can easily be generalized to establish an even stronger relational property— representation independence —for realistic type systems.

Safety comparison of single-donor and pooled fecal microbiota transfer product preparation in ulcerative colitis: systematic review and meta-analysis

BackgroundMultiple studies have evaluated fecal microbiota transfer (FMT) in patients with ulcerative colitis (UC) using single-donor (SDN) and multidonor (MDN) products. Systematic review and meta-analysis were performed to compare the safety of SDN and MDN products.MethodsSystematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence to identify studies that compared FMT products manufactured using SDN or MDN strategies against control treatment in patients with UC. Fifteen controlled studies were selected for meta-analysis (11 randomized controlled trials and 4 controlled cohort trials). Safety of each treatment type was assessed using the counts of adverse events and serious adverse events using fixed- and random-effects models. Significance of the indirect difference between FMT preparations was assessed using a network approach. Benefit-risk ratios were calculated by multiplicative utility model, incorporating geometric mean of risk ratios (RRs) of efficacy and safety.ResultsSafety data was collected for a total of 587 patients (193 exposed to SDN products, 114 exposed to MDN products and 280 exposed to control treatment). The 12 studies showed similar overall safety event counts for MDN and SDN versus placebo (RRs: 0.90 and 1.09, respectively [P = 0.206 and P = 0.420, respectively]). Results indicated similar risk of safety events for MDN compared to SDN (RR: 0.83, P = 0.159). Positive benefit-risk ratios were demonstrated for MDN and SDN versus placebo (RRs: 1.70 and 1.16, respectively [P = 0.003 and P = 0.173, respectively]). MDN had a greater benefit-risk ratio compared to SDN (RR: 1.46, P = 0.072).ConclusionSimilar safety profiles were observed for MDN and SDN strategies. Alongside previously described superior efficacy, treatment with MDN has greater benefit-risk ratio than SDN in patients with UC. Further development of MDN FMT treatment for UC should be considered.

Combining Type Checking and Set Constraint Solving to Improve Automated Software Verification

Abstract This technical note shows how we have combined prescriptive type checking and constraint solving to increase automation during software verification. We do so by defining a type system and implementing a typechecker for $\{log\}$ (read ‘setlog’), a Constraint Logic Programming language and satisfiability solver based on set theory. The constraint solver is proved to be safe w.r.t. the type system. Two industrial-strength case studies are presented where this combination is used with very good results.

Atrasentan in Patients with IgA Nephropathy.

Patients with IgA nephropathy and severe proteinuria have a high lifetime risk of kidney failure. The efficacy and safety of the selective endothelin type A receptor antagonist atrasentan in reducing proteinuria in patients with IgA nephropathy are incompletely understood. We are conducting a phase 3, multinational, double-blind, randomized, controlled trial involving adults with biopsy-proven IgA nephropathy, a total urinary protein excretion of at least 1 g per day, and an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m2 of body-surface area. Patients were randomly assigned to receive atrasentan (0.75 mg per day) or matched placebo for 132 weeks. The primary outcome, assessed at a prespecified interim analysis of data from the first 270 patients in the main stratum, was the change in the 24-hour urinary protein-to-creatinine ratio from baseline to week 36; the change was estimated with the use of a repeated-measures model. (An exploratory stratum of patients who were receiving a sodium-glucose cotransporter 2 inhibitor were included in a separate analysis.) Safety analyses were based on adverse events across the entire main stratum. A total of 340 patients were recruited into the main stratum. Among the first 270 patients in the main stratum (135 per trial group) who completed the week 36 visit, the geometric mean percentage change in the urinary protein-to-creatinine ratio relative to baseline was significantly greater with atrasentan (-38.1%) than with placebo (-3.1%), with a geometric mean between-group difference of -36.1 percentage points (95% confidence interval, -44.6 to -26.4; P<0.001). The percentage of patients with adverse events did not differ substantially between the two groups. Fluid retention was reported by 19 of 169 patients (11.2%) in the atrasentan group and in 14 of 170 (8.2%) in the placebo group but did not lead to discontinuation of the trial regimen. No apparent cases of cardiac failure or severe edema occurred. In this prespecified interim analysis, atrasentan resulted in a significant and clinically meaningful reduction in proteinuria as compared with placebo in patients with IgA nephropathy. (Funded by Novartis; ALIGN ClinicalTrials.gov number, NCT04573478.).

Refinement Type Refutations

Refinement types combine SMT decidable constraints with a compositional, syntax-directed type system to provide a convenient way to statically and automatically check properties of programs. However, when type checking fails, programmers must use cryptic error messages that, at best, point out the code location where a subtyping constraint failed to determine the root cause of the failure. In this paper, we introduce refinement type refutations, a new approach to explaining why refinement type checking fails, which mirrors the compositional way in which refinement type checking is carried out. First, we show how to systematically transform standard bidirectional type checking rules to obtain refutations. Second, we extend the approach to account for global constraint-based refinement inference via the notion of a must-instantiation: a set of concrete inhabitants of the types of subterms that suffice to demonstrate why typing fails. Third, we implement our method in HayStack—an extension to LiqidHaskell which automatically finds type-refutations when refinement type checking fails, and helps users understand refutations via an interactive user-interface. Finally, we present an empirical evaluation of HayStack using the regression benchmark-set of LiqidHaskell, and the benchmark set of G2, a previous method that searches for (non-compositional) counterexample traces by symbolically executing Haskell source. We show that HayStack can find refutations for 99.7% of benchmarks, including those with complex typing constructs (e.g., abstract and bounded refinements, and reflection), and does so, an order of magnitude faster than G2.

Imperative Compositional Programming: Type Sound Distributive Intersection Subtyping with References via Bidirectional Typing

Compositional programming is a programming paradigm that emphasizes modularity and is implemented in the CP programming language. The foundations for compositional programming are based on a purely functional variant of System F with intersection types, called Fi+, which includes distributivity rules for subtyping. This paper shows how to extend compositional programming and CP with mutable references, enabling a modular, imperative compositional programming style. A technical obstacle solved in our work is the interaction between distributive intersection subtyping and mutable references. Davies and Pfenning [2000] studied this problem in standard formulations of intersection type systems and argued that, when combined with references, distributive subtyping rules lead to type unsoundness. To recover type soundness, they proposed dropping distributivity rules in subtyping. CP cannot adopt this solution, since it fundamentally relies on distributivity for modularity. Therefore, we revisit the problem and show that, by adopting bidirectional typing, a more lightweight and type sound restriction is possible: we can simply restrict the typing rule for references. This solution retains distributivity and an unrestricted intersection introduction rule. We present a first calculus, based on Davies and Pfenning's work, which illustrates the generality of our solution. Then we present an extension of Fi+ with references, which adopts our restriction and enables imperative compositional programming. We implement an extension of CP with references and show how to model a modular live-variable analysis in CP. Both calculi and their proofs are formalized in the Coq proof assistant.

CoolerSpace: A Language for Physically Correct and Computationally Efficient Color Programming

Color programmers manipulate lights, materials, and the resulting colors from light-material interactions. Existing libraries for color programming provide only a thin layer of abstraction around matrix operations. Color programs are, thus, vulnerable to bugs arising from mathematically permissible but physically meaningless matrix computations. Correct implementations are difficult to write and optimize. We introduce CoolerSpace to facilitate physically correct and computationally efficient color programming. CoolerSpace raises the level of abstraction of color programming by allowing programmers to focus on describing the logic of color physics. Correctness and efficiency are handled by CoolerSpace. The type system in CoolerSpace assigns physical meaning and dimensions to user-defined objects. The typing rules permit only legal computations informed by color physics and perception. Along with type checking, CoolerSpace also generates performance-optimized programs using equality saturation. CoolerSpace is implemented as a Python library and compiles to ONNX, a common intermediate representation for tensor computations. CoolerSpace not only prevents common errors in color programming, but also does so without run-time overhead: even unoptimized CoolerSpace programs out-perform existing Python-based color programming systems by up to 5.7 times; our optimizations provide up to an additional 1.4 times speed-up.

A Dependent Nominal Physical Type System for Static Analysis of Memory in Low Level Code

We tackle the problem of checking non-proof-carrying code , i.e. automatically proving type-safety (implying in our type system spatial memory safety) of low-level C code or of machine code resulting from its compilation without modification. This requires a precise static analysis that we obtain by having a type system which (i) is expressive enough to encode common low-level idioms, like pointer arithmetic, discriminating variants by bit-stealing on aligned pointers, storing the size and the base address of a buffer in distinct parts of the memory, or records with flexible array members, among others; and (ii) can be embedded in an abstract interpreter. We propose a new type system that meets these criteria. The distinguishing feature of this type system is a nominal organization of contiguous memory regions, which (i) allows nesting, concatenation, union, and sharing parameters between regions; (ii) induces a lattice over sets of addresses from the type definitions; and (iii) permits updates to memory cells that change their type without requiring one to control aliasing. We provide a semantic model for our type system, which enables us to derive sound type checking rules by abstract interpretation, then to integrate these rules as an abstract domain in a standard flow-sensitive static analysis. Our experiments on various challenging benchmarks show that semantic type-checking using this expressive type system generally succeeds in proving type safety and spatial memory safety of C and machine code programs without modification, using only user-provided function prototypes.

On the Expressive Power of Languages for Static Variability

Variability permeates software development to satisfy ever-changing requirements and mass-customization needs. A prime example is the Linux kernel, which employs the C preprocessor to specify a set of related but distinct kernel variants. To study, analyze, and verify variational software, several formal languages have been proposed. For example, the choice calculus has been successfully applied for type checking and symbolic execution of configurable software, while other formalisms have been used for variational model checking, change impact analysis, among other use cases. Yet, these languages have not been formally compared, hence, little is known about their relationships. Crucially, it is unclear to what extent one language subsumes another, how research results from one language can be applied to other languages, and which language is suitable for which purpose or domain. In this paper, we propose a formal framework to compare the expressive power of languages for static (i.e., compile-time) variability. By establishing a common semantic domain to capture a widely used intuition of explicit variability, we can formulate the basic, yet to date neglected, properties of soundness, completeness, and expressiveness for variability languages. We then prove the (un)soundness and (in)completeness of a range of existing languages, and relate their ability to express the same variational systems. We implement our framework as an extensible open source Agda library in which proofs act as correct compilers between languages or differencing algorithms. We find different levels of expressiveness as well as complete and incomplete languages w.r.t. our unified semantic domain, with the choice calculus being among the most expressive languages.

Making Formulog Fast: An Argument for Unconventional Datalog Evaluation

With its combination of Datalog, SMT solving, and functional programming, the language Formulog provides an appealing mix of features for implementing SMT-based static analyses (e.g., refinement type checking, symbolic execution) in a natural, declarative way. At the same time, the performance of its custom Datalog solver can be an impediment to using Formulog beyond prototyping—a common problem for Datalog variants that aspire to solve large problem instances. In this work we speed up Formulog evaluation, with some surprising results: while 2.2× speedups can be obtained by using the conventional techniques for high-performance Datalog (e.g., compilation, specialized data structures), the big wins come by abandoning the central assumption in modern performant Datalog engines, semi-naive Datalog evaluation. In the place of semi-naive evaluation, we develop eager evaluation, a concurrent Datalog evaluation algorithm that explores the logical inference space via a depth-first traversal order. In practice, eager evaluation leads to an advantageous distribution of Formulog’s SMT workload to external SMT solvers and improved SMT solving times: our eager evaluation extensions to the Formulog interpreter and Soufflé’s code generator achieve mean 5.2× and 7.6× speedups, respectively, over the optimized code generated by off-the-shelf Soufflé on SMT-heavy Formulog benchmarks. All in all, using compilation and eager evaluation (as appropriate), Formulog implementations of refinement type checking, bottom-up pointer analysis, and symbolic execution achieve speedups on 20 out of 23 benchmarks over previously published, hand-tuned analyses written in F ♯ , Java, and C++, providing strong evidence that Formulog can be the basis of a realistic platform for SMT-based static analysis. Moreover, our experience adds nuance to the conventional wisdom that traditional semi-naive evaluation is the one-size-fits-all best Datalog evaluation algorithm for static analysis workloads.

Law and Order for Typestate with Borrowing

Typestate systems are notoriously complex as they require sophisticated machinery for tracking aliasing. We propose a new, transition-oriented foundation for typestate in the setting of impure functional programming. Our approach relies on ordered types for simple alias tracking and its formalization draws on work on bunched implications. Yet, we support a flexible notion of borrowing in the presence of typestate. Our core calculus comes with a notion of resource types indexed by an ordered partial monoid that models abstract state transitions. We prove syntactic type soundness with respect to a resource-instrumented semantics. We give an algorithmic version of our type system and prove its soundness. Algorithmic typing facilitates a simple surface language that does not expose tedious details of ordered types. We implemented a typechecker for the surface language along with an interpreter for the core language.

Efficacy of Interalesional Botulinum Toxin Type A vs Cryotherapy in Treatment of Keloids: Comparative Clinical, Histopathological and Immunohistochemical Study

Abstract Background Keloid is a common dermatological complaint produced by disruption of the normal wound healing process. Several treatment modalities for keloids are available with variable degrees of response such as surgical excision, topical and intralesional corticosteroids, interferon, botulinum toxin, cryotherapy and laser therapy. Aim of the Study The aim of the present study is to compare the clinical efficacy and safety of intralesional botulinum toxin type A and cryotherapy in the treatment of keloids. Patients and Methods This study included 10 patients complaining of keloids (at least 2 lesions). Keloids were treated by either cryotherapy (one session every two weeks) or intralesional BTX-A (5 IU/cm2 once every 4 weeks). Punch biopsy was done for every lesion before the start of treatment and repeated 4 weeks after the end of treatment. Results Both treatment modalities achieved statistically significant clinical response (keloid pliability, height and VSS score) histological response (epidermal thickness) and immunohistochemical response (fibronectin spot count). Both treatments were well tolerated and satisfying to included patients.

Main heat transport system configuration influence on steam drum level control and safety for a pressure tube type boiling water reactor with multiple interconnected loops

Abstract NCABWR (Natural-Circulation-Advanced-Boiling-Water-Reactor) is a pressure-tube-type BWR with multiple inter-connected Main-Heat-Transport (MHT) system loops and steam drums (SDs). SD-Level-Control is related to, the MHT coolant inventory and sustained heat removal, hence the overall safety of the Nuclear-Power-Plant (NPP). SD-Level is vital for ensuring presence of adequate coolant-inventory with sufficient and prolonged cooling of fuel, for normal-operation and accidents. In the initial-MHT-configuration of NCABWR the four MHT-loops are, inter-connected at the Common-Reactor-Inlet-Header (CRIH), which influences the SDLC adversely; such occurrences are, not reported in the open literature. Open loop (without SD-level-controllers) step-change response showed that initial MHT-configuration response is stable, non-oscillatory and non-diverging even for a high-magnitude step-change in the feed-flows. Closed-loop (with SD-level-controllers) response, even to minor disturbances leads to diverging SD-Levels due to CRIH-MHT-configuration (Gaikwad, A.J., Vijayan, P., Iyer, K., Bhartiya, S., Kumar, R., Lele, H.G., Ghosh, A.K., Kushwaha, H.S., and Sinha, R.K. (2009). Effect of loop configuration on steam drum level control for a multiple drum interconnected loops pressure tube type boiling water reactor. IEEE Trans. Nucl. Sci. 56: 3712–3725). CRIH is required to overcome Postulated-Initiating-Event (PIE) for single-accumulator-failure-LOCA. A hypothetical MHT-configuration with partitioning of CRIH will isolate each loop from one another and lead to a stable SDLC, but then for the above-mentioned PIE safety is not met. LOCA in one of the four ECCS header-compartments require a mandatory interconnection among, the four MHT-Loops at CRIH. Solution to SDLC issue were explored with changes in MHT-configuration and with innovative solution-schemes for feed-water-system and SDLCs. In the present study the pioneering solution-schemes with individual SD pressure control for SD level control and the Split/Double baffle are proposed, implemented and the performance was tested with simulation are discussed in details with other solution schemes.

Higher-Order Asynchronous Effects

We explore asynchronous programming with algebraic effects. We complement their conventional synchronous treatment by showing how to naturally also accommodate asynchrony within them, namely, by decoupling the execution of operation calls into signalling that an operation's implementation needs to be executed, and interrupting a running computation with the operation's result, to which the computation can react by installing interrupt handlers. We formalise these ideas in a small core calculus and demonstrate its flexibility using examples ranging from a multi-party web application, to pre-emptive multi-threading, to (cancellable) remote function calls, to a parallel variant of runners of algebraic effects. In addition, the paper is accompanied by a formalisation of the calculus's type safety proofs in Agda, and a prototype implementation in OCaml.

Volatilomics: An emerging discipline within Omics Sciences - A systematic review

Introduction Volatilomics is an omics science that is characterized as being a specific subbranch of metabolomics, which studies the different types of volatile organic compounds that may be present in a certain biological matrix. It has had impacts on the identification of new natural compounds and food safety processes, since it allows the evaluation of emerging contaminants that are present on food matrices, through the identification of biomarkers generated in response to this type of xenobiotic compounds through xenovolatilomic studies. Objective In this way, this review seeks to understand the scientific advances reported towards volatilomic studies, for which different types of primary research are reported depending on the main instrumental techniques used for the characterization of different types of VOCs that have been reported in our country between 2012 and 2022. Methodology Using a qualitative methodology, a search was carried out in the Scopus database, from which the bibliometric information of the primary research reported during this time was obtained, to later analyze the different research concerning the use of volatilomic studies and the fields of action that are currently used, as well as the different techniques for obtaining these compounds and the data analysis methodologies established for the processing of this type of research. Conclusions Finally, it can be concluded that, from the present review, the applicability of volatilomic studies is shown. The incursion carried out by this type of science on the verification of food safety in different types of matrices, in addition to allowing the study of the volatile profile formed by the different volatile organic compounds expressed by said matrix and the respective ecological role expressed by these compounds with the environment in which they are found.

12-year effectiveness and safety of botulinum toxin type A for the treatment of blepharospasm and hemifacial spasm

12-year effectiveness and safety of botulinum toxin type A for the treatment of blepharospasm and hemifacial spasm

Assessing the efficacy and quality of Life improvements of botulinum toxin type a with topical minoxidil versus topical minoxidil in male androgenetic alopecia: a randomized controlled trial.

Androgenetic alopecia (AGA) is a common type of hair loss in men and efficacy and safety of current medical treatment remain limited. Therefore, the present study aimed to investigate the efficacy and safety of botulinum toxin type A (BTA) combined with Minoxidil in patients with AGA. 60 male patients were included in this study and control group received topical 5% Minoxidil and the treatment group received BTA combined with topical 5% Minoxidil. BTA injections (60-70 U) were administered at 30-35 scalp sites. Head photographs were taken at baseline, 2nd, 4th, and 6th months. Clinical descriptions recorded scalp conditions, and patient satisfaction along with Dermatology Life Quality Index scores were documented. The treatment group (TG) showed significant hair growth differences compared to the control group (CG) at the 4th month (P < 0.001) and 6th month (P = 0.0046) post-treatment. TG had improved Investigator Global Assessment (IGA) scores in the 4th month (P = 0.0001) and 6th month (P = 0.0259) compared to CG. Patient satisfaction in TG for hair growth and scalp improvement was higher than CG (all P < 0.05). TG exhibited substantial quality of life improvement at the 4-month (P = 0.0009) and 6-month (P = 0.0099). No adverse reactions were observed post-botulinum toxin injection. BTA combined with Minoxidil effectively promotes hair growth, enhances the quality of life, and alleviates scalp symptoms in male AGA patients at 4th and 6th months, with no adverse effects compared to Minoxidil alone.Trial registration number: Ethics Committee of Shanghai Tongji Hospital (ID: K-2018-026).